A Novel Automatic Quantification Protocol for Biomarkers of Tauopathies in the Hippocampus and Entorhinal Cortex of Post-Mortem Samples Using an Extended Semi-Siamese U-Net

Abstract

Efforts have been made to diagnose and predict the course of different neurodegenerative diseases through various imaging techniques. Particularly tauopathies, where the tau polypeptide is a key participant in molecular pathogenesis, have significantly increased their morbidity and mortality in the human population over the years. However, the standard approach to exploring the phenomenon of neurodegeneration in tauopathies has not been directed at understanding the molecular mechanism that causes the aberrant polymeric and fibrillar behavior of the tau protein, which forms neurofibrillary tangles that replace neuronal populations in the hippocampal and cortical regions. The main objective of this work is to implement a novel quantification protocol for different biomarkers based on pathological post-translational modifications undergone by tau in the brains of patients with tauopathies. The quantification protocol consists of an adaptation of the U-Net neural network architecture. We used the resulting segmentation masks for the quantification of combined fluorescent signals of the different molecular changes tau underwent in neurofibrillary tangles. The quantification considers the neurofibrillary tangles as an individual study structure separated from the rest of the quadrant present in the images. This allows us to detect unconventional interaction signals between the different biomarkers. Our algorithm provides information that will be fundamental to understanding the pathogenesis of dementias with another computational analysis approach in subsequent studies.